Functional evidence for heterogeneity of peripheral prejunctional α 2 ‐adrenoceptors

1 We have examined the potencies of a series of α 2 ‐adrenoceptor antagonists in functional studies of prejunctional α 2 ‐adrenoceptors in rat atrium and vas deferens, and compared potencies with affinities for the α 2A ‐ligand binding site of human platelet and the α 2B ‐ site of rat kidney. 2 Antagonist potency in rat atrium was expressed as an EC 30 (concentration producing 30% increase in the stimulation‐evoked overflow of tritium in tissues pre‐incubated with [ 3 H]‐noradrenaline). Antagonist potency in rat vas deferens was expressed as a pA 2 or K B at antagonizing the inhibition by the α 2 ‐adrenoceptor agonist xylazine of the isometric twitch to a single stimulus, or as an EC 30 . 3 In ligand binding studies, K i values were obtained for the displacement by α‐adrenoceptor antagonists of [ 3 H]‐yohimbine binding to human platelet or rat kidney membranes. 4 In functional studies, three antagonists (ARC 239, prazosin and chlorpromazine) distinguished between prejunctional α 2 ‐adrenoceptors of rat atrium (EC 30 ) and rat vas deferens (pA 2 ) and showed 49, 12 and 7 times higher potency in rat atrium, respectively. ARC 239 was also 17 times more potent in rat atrium than rat vas deferens when EC 30 values were compared. 5 The correlation of affinity for the α 2A ‐ site of human platelet was better with prejunctional potency in rat vas deferens than rat atrium. 6 The correlation of affinity for the α 2B ‐site of rat kidney was better with prejunctional potency in rat atrium than rat vas deferens. 7 It is concluded that prejunctional α 2 ‐adrenoceptors of rat vas deferens and rat atrium differ, and these receptors may resemble the α 2A ‐ and α 2B ‐ligand binding sites, respectively.